DESCRIPTION: (Applicant's Description) Advanced image-guidance techniques promise to revolutionize external beam radiation therapy of prostate cancer. A major roadblock to the full exploitation of radiation's therapeutic effect is the lack of geometric precision that can be maintained over the fractionated course of therapy. The motivation for increased precision is clear: by increasing the precision of field placement, the prostate can be confidently irradiated with a smaller and more conformal radiation field, thereby reducing the probability of complications in surrounding normal tissues. The reduced probability of complication allows the oncologist to pursue higher radiation doses, thereby improving efficacy while maintaining complication rates at a manageable level. In this combined R21/R33 proposal, a method to dramatically increase the precision of radiation field delivery through image-guidance is described, and a clinical approach for high-precision radiotherapy of the prostate is proposed. The cornerstone of this approach is a kilovoltage (kV) cone-beam computed tomography (CT) scanner that is integrated onto the gantry of a medical linear accelerator. This innovative combination permits tomographic imaging of the prostate and normal structures in the treatment reference frame. Ideally, a real-time inverse plan for treatment delivery would be generated and delivered within moments of imaging. While technology exists to perform the inverse planning step, it does not yet permit it to be performed in an on-line fashion. This limitation should not prevent the pursuit of on-line treatment planning and delivery. In this proposal, a simplified approach is adopted to permit on-line image-guided radiotherapy of the prostate within a 30 minute time interval. In the R21 phase of this proposal, the clinical feasibility and the limitations of such an approach will be quantified by studying the probability and magnitude of patient motion over the time frame of radiation delivery using cine-MR imaging. The need to minimize the time between imaging and delivery also requires fast prostate delineation. A set of proposed methods to reduce the time required for prostate delineation will be tested. The results of these two aims will establish the inherent geometric limitations that can be achieved with image-guidance. In the R33 phase, a system for on-line image-guidance is constructed based upon a conventional accelerator, cone-beam CT imaging, and a conventional planning system. Each of these components is adapted to provide an integrated system to deliver high-precision image-guided radiotherapy of the prostate in less than 30 minutes. The completion of this system will provide radiation oncologists with the opportunity for unprecedented geometric precision in non-invasive therapy of the prostate.